Polypharmacy in Hypertension Management: Clinical Challenges and Drug-Drug Interactions: A Narrative Review

The management of hypertension often requires multidrug therapy (polypharmacy), which increases the risk of clinically significant drug-drug interactions (DDIs) and related adverse effects. This narrative review aims to summarize recent evidence on the clinical challenges associated with polypharmacy in hypertension management, with a particular focus on drug–drug interactions and their implications for patient safety and treatment outcomes. A literature search was conducted using major databases, including PubMed, Google Scholar, and ScienceDirect, covering publications from 2020 to 2025. The findings highlight that polypharmacy contributes to increased healthcare burden through adverse drug events, hospitalizations, and decreased treatment adherence, such as additive hypotensive effects, interference with drug metabolism (e.g., via cytochrome P450), altered renal handling, and antagonistic effects between agents. Clinically, DDIs may lead to hypotension, renal impairment, electrolyte disturbances, and reduced therapeutic efficacy. Vulnerable groups include older adults, those with renal dysfunction, and patients on multiple classes of antihypertensive or with comorbidities requiring additional drugs. Effective management strategies include regular medication review, deprescribing when appropriate, use of fixed-dose combinations, clinical decision support systems, and pharmacist-led interventions. Polypharmacy is a double-edged sword in hypertension management: while often necessary for adequate control, it carries a substantial risk of harmful DDIs. Clinicians should proactively evaluate and manage interaction risk, balance benefit versus harm in prescribing decisions, and personalize therapy.